1. Field of the Invention
This invention uses the unequal pharmacological activities (both for toxic events and therapeutic events) and the different pharmacokinetics of the enantiomers of verapamil as a basis for customizing the administered verapamil enantiomer mixture to produce a desired verapamil enantiomer ratio in the plasma or serum of patients.
2. Brief Description of the Prior Art
Verapamil, benzeneacetonitrile, .alpha.-3-2-(3,4-dimethoxyphenyl)ethyl!methylamino!propyl!-3,4-dimethox y-.alpha.-(1-methylethyl) hydrochloride, is a commercially available drug. It is a calcium ion influx inhibitor (slow channel blocker or calcium ion antagonist).
Current marketed verapamil dosage forms intended for cardiovascular therapy contain equal amounts of R-verapamil and S-verapamil. When administered intravenously this mixture produces circulating R-verapamil concentrations that are approximately twice the S-verapamil concentrations. When administered orally as an immediate release formulation, this mixture produces approximately a 3:1 R:S ratio in the systemic circulation; as an oral sustained release formulation the plasma ratio is approximately 5:1. Thus a single chemical composition produces chemically dissimilar plasma concentrations, and pharmacologically dissimilar effects depending on the route of administration, and the type of formulation used.
It is an object of the present invention to provide consistent dosage effects by tailoring the enantiomeric composition (i.e., the enantiomeric ratio) of the administered dosage form to the route of administration and/or the rate of drug release.
It is another object of the present invention to manipulate the enantiomeric ratio of the administered drug based on formulation and route of administration to yield systemic plasma enantiomer concentration ratios that are associated with desired risk-benefit ratios for a targeted indication.